MRNA sequencing of single-cell and 20-cell pools of CD103+CD8+ and CD103-CD8+ T lymphocytes sorted from human ovarian cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA525699 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8671320.fastq.gz | Fastqsanger.gz | |||
| SRR8671330.fastq.gz | Fastqsanger.gz | |||
| SRR8671340.fastq.gz | Fastqsanger.gz | |||
| SRR8671350.fastq.gz | Fastqsanger.gz | |||
| SRR8671360.fastq.gz | Fastqsanger.gz |
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Project description:Cytotoxic T cells confer a prognostic benefit in many tumors, including ovarian cancer. We and others have previously identified a subset of CD8+ T cells, namely CD103+CD8+ T cells, that seems to have a better prognostic effect. The aim of this study is to identify how these CD103+ T cells differ from CD103-CD8+ T cells on mRNA level in human samples of ovarian cancer.
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Project description:We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells.
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Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride
Project description:Initially identified as a functional marker for resident-memory (Trm) CD8+ T cells, CD103 (encoded by ITGAE gene) has broad roles in immunity and diseases. Elucidating the function and regulation of CD103 is thus of importance. This study revealed that the CD103 expression by CD8 T cells under steady state contributes to the clearance of acute viral infection. More importantly, it discovered TGF-SKI-Smad4 a critical signaling axis in restricting CD103 expression in CD8+ T cells for their function. Mechanistically, by ChIP-Seq and ChIP analysis, SKI associated with Smad4 was found to directly and epigenetically suppress CD103 transcription. This study therefore reveals a novel TGF-SKI-Smad4 pathway to specifically enable CD103 expression in CD8+ T cells for protective immunity.
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Project description:CD8 tissue-resident memory T (TRM) cells provide front-line protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.
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Project description:Immunotherapies have had unprecedented success for multiple cancer types, albeit with variable response rates. Unravelling the complex network of immune cells within the tumour microenvironment (TME) may provide additional insights to enhance anti-tumour immunity and improve clinical response. Here, we identified a CD103-expressing CD56+ ILC subset that were associated with a poor proliferative capacity of tumour-infiltrating lymphocytes (TILs) in culture. We demonstrate that CD103+CD56+ ILCs isolated directly from tumors represent a distinct ILC population that expressed unique surface markers, transcription factor networks, and transcriptomic profiles compared to CD103-CD56+ NK cells. Using multiple approaches, we found that these CD103+CD56+ ILCs were associated with CD8+ T cells with a reduced expression of GZMB. This study identifies 59 a population of CD103+CD56+ ILCs with potentially inhibitory functions, that are associated with a TME that includes CD8+ T cells with poor anti-tumour activity. Further studies focusing on these potentially inhibitory cells may provide insights into understanding the biology of an inhibitory TME.
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